Ubiquitin in the activation and attenuation of innate antiviral immunity

Heaton, Steven M.; Borg, Natalie A.; Dixit, Vishva M.

The innate immune signaling architecture is complex and has coevolved with the pathogens it guards against, meanwhile restraining autoimmunity through an elaborate negative feedback scheme. A cornerstone of this dynamic regulatory framework is the ubiquitin modification system, which is manipulated by viruses relevant to human disease. Going forward in understanding mechanisms of infection and autoimmunity, we must address significant gaps in knowledge regarding the specificity and context-dependent regulation of E3s and DUbs and the consequences of ubiquitin modification. This will expose further cross-talk between the immune signaling cascades, revealing a functional and self-regulating whole. In the search for a new generation of antiviral and autoimmune treatments, we continue to learn from the pathogens that have long adapted to exploit this ready-made system of functional regulation; humans possess hundreds of specific-and general-effect E3s and DUbs, many of which could be harnessed for therapeutic use.